Since the beginning of RHD genotyping in maternal plasma, no Rh D positive baby was diagnosed RHD negative in our institution. Genotyping from circulating DNA in maternal plasma is as efficient as ... [more ▼]

Since the beginning of RHD genotyping in maternal plasma, no Rh D positive baby was diagnosed RHD negative in our institution. Genotyping from circulating DNA in maternal plasma is as efficient as genotyping on amniocyts but without the associated risks. We propose a prophylactic injection based on fetal genotyping RHD in maternal blood with 300 microg anti-D immunoglobulin at 28 weeks of amenhorrea in all of Rh D negative pregnant women whitch fetuses positive RHD. [less ▲]

Despite generalisation of anti-D immunoprophylaxis, RhD allo-immunisation still remains the major cause of severe haemolytic disease of the fetus and of the newborn (HDFN). The routine follow up of ... [more ▼]

Despite generalisation of anti-D immunoprophylaxis, RhD allo-immunisation still remains the major cause of severe haemolytic disease of the fetus and of the newborn (HDFN). The routine follow up of pregnant women comprises: the ABO/D, Rh/Kell red cells typing and the search for irregular antibodies. In case of anti-D immunisation, the paternal Rh phenotype, when known, provides useful information regarding the probability for the fetus to have inherited the D antigen and thereby to be exposed to the risk of HDFN. The antibody titre, which is predictive of possible in vivo haemolysis, must be interpreted in the light of the previous obstetric history, and can lead to the decision of invasive amniocentesis. Then the measurement of the optical density (deltaOD450 nm) and the fetal RhD typing can be realised on amniotic fluid. New molecular techniques make it possible now to demonstrate the presence of fetal DNA in maternal plasma. These methods lying on non invasive procedures could advantageously be applied to the genotyping of fetal RHD during pregnancy. The present paper aims to discuss the predictive values of RHD fetal genotype in maternal plasma of RhD negative mothers. The ante-partum management of immunised pregnant women is reviewed in the light of this new molecular approach combined to Doppler ultrasonography of the fetal middle cerebral artery. This non invasive method for determining fetal RHD genotype could be systematically proposed to all RhD negative pregnant women for a better targeted prenatal follow-up and an increased efficacy of RhD prophylaxis. [less ▲]

OBJECTIVES: To evaluate the predictive value of RHD fetal genotype in maternal plasma of Rh D negative mothers after 10 weeks of gestation in a clinical use. MATERIAL AND METHOD: Prospective, comparative study between fetal RHD genotyping in maternal plasma, with amplification of exons 4,5,10 of the RHD gene, by real-time multiplex PCR, and Rh D serology at birth, in 218 pregnancy and their 223 babies, between November 2002 and 2004. RESULTS: Combining the amplification of three exons, the concordance rate of fetal Rh D genotyping in maternal plasma and baby phenotyping at delivery was 100%. Four women whose the babies were Rh D negative were positive for RHD exon 10 during pregnancy. This positivity was, in three cases, correlated with the presence of RHDpsi pseudogene and in last case, with a haplotype Cdes (r's). RHD genotyping was performed for five twin pregnancies. CONCLUSION: Multiplex PCR using maternal plasma provides perfect prenatal prediction of fetal RHD gene. These results confirm that this non invasive procedure is the preferred method for assessing Rh D fetal status in Rh negative mothers. Using this method for two years in routine practice has led us to modify our management scheme for sensitized Rh D-negative pregnant women. [less ▲]

in American Journal of Obstetrics and Gynecology (2005), 192(1), 323-332

Objective: It is supposed that the intervillous space. is not perfused by maternal blood during the first trimester, suggesting vascular shunts in the myometrium. We therefore attempted to provide ... [more ▼]

Objective: It is supposed that the intervillous space. is not perfused by maternal blood during the first trimester, suggesting vascular shunts in the myometrium. We therefore attempted to provide arguments for a functional vascular anastomotic network located in the placental bed during human pregnancy. Study design: Three-dimensional (3D) sonogyraphy, laboratory analyses. and anatomic studies (hysterectomy specimens, uteroplacental vascular cast) were performed. Results: Color Doppler showed a vascular network with anastomotic aspect located in the placental bed. A vascular cast of a uterus. obtained after postpartum hemorrhage. demonstrated a vascular anastomotic network in the myometrium. Higher Po-2 levels in the uterine vein compared with the intervillous space confirmed the functional nature of this Shunt. Low resistances in the uterine arteries during the first week after delivery suggested that this vascular network remains functional after placental expulsion. Conclusion: Our studies have yielded functional and anatomic evidence of an arteriovenous Shunt located in the subplacental myometrium. (C) 2005 Elsevier Inc. All rights reserved. [less ▲]

in Journal of Clinical Endocrinology and Metabolism (2003), 88(11), 5555-5563

Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in ... [more ▼]

Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in the VEGF family may explain the defective uteroplacental vascularization characterizing preeclampsia. We compared pregnancies complicated by early onset severe preeclampsia or intrauterine growth retardation to normal pregnancies. Maternal plasma, placentas, and placental bed biopsies were collected. The mRNA levels of VEGF-A, PlGF, and their receptors were quantified in placentas and placental beds. Levels of VEGF-A, PlGF, and soluble VEGF receptor (VEGFR) were assessed in maternal plasma. In compromised pregnancies, elevated levels of VEGF-A and VEGFR-1 mRNAs may reflect the hypoxic status of the placenta. On contrast, the membrane-bound VEGFR-1 was decreased in the placental bed of preeclamptic patients. Preeclampsia was associated with low levels of circulating PlGF and increased levels of total VEGF-A and soluble VEGFR-1. Free VEGF-A was undetectable in maternal blood. Immunohistochemical studies revealed that VEGF-A and PlGF were localized in trophoblastic cells. Altogether, our results suggest two different pathophysiological mechanisms associated with preeclampsia. The first one is related to an overproduction of competitive soluble VEGFR-1 that may lead to suppression of VEGF-A and PlGF effects. The second one is the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, which may result in the defective uteroplacental development. [less ▲]

The object of the study was to investigate the outcome in growth-retarded newborns who were diagnosed with fetal renal hyperechogenicity without anatomical abnormality during any stage of pregnancy ... [more ▼]

The object of the study was to investigate the outcome in growth-retarded newborns who were diagnosed with fetal renal hyperechogenicity without anatomical abnormality during any stage of pregnancy. Depending on the fetal renal ultrasonography result, the cases were divided into two study groups. There was an intrauterine growth-retarded group with fetal renal medullary hyperechogenicity and another group without fetal renal medullary hyperechogenicity. The renal parenchyma was observed after birth, within the first 5 days of life, and several times until the 14th postpartum day in positive cases. Hyperechogenic renal medullae were detected in 25 of 90 cases with intrauterine growth retardation during the 8-month study period. This may be an in utero cause of subsequent intrauterine and neonatal complications, such as cesarean section because of fetal distress (36%), perinatal infection (24%), treatment in a neonatal intensive care unit (52%), or increased perinatal mortality (8%). The results demonstrate that fetuses with hyperechoic medullae had 1.5 times the risk of an abnormal outcome compared with fetuses with normal echoic kidneys and intrauterine growth retardation. Detailed ultrasound examinations of renal parenchyma appear to be useful for the prenatal diagnosis of intrauterine hypoxia, allowing the detection of possible pathological fetal conditions in utero. [less ▲]

The object of this study was to investigate the fetal renal arterial blood flow in normal and hyperechogenic kidneys during the third trimester of gestation. The pregnancies screened were all chronically ... [more ▼]

The object of this study was to investigate the fetal renal arterial blood flow in normal and hyperechogenic kidneys during the third trimester of gestation. The pregnancies screened were all chronically hypoxic. Depending on the etiology of the intrauterine chronic hypoxia, the cases were divided into two study groups. Group I comprised 120 pregnant women with pregnancy-associated hypertension and/or proteinuria. Group II consisted of 87 pregnancies with intrauterine growth retardation. Both study groups included pregnant women from the third trimester. Hyperechogenic renal medullae were detected in 15 out of 120 cases with pregnancy-associated hypertension and/or proteinuria, and in 22 fetuses of the 87 pregnancies involving intrauterine growth retardation. Fetal renal hyperechogenicity appears to be an indicator of fetal arterial circulatory depression, correlated with pathological changes in the resistance index for the fetal renal arteries. The fetal renal arterial blood flow resistance index was significantly lower in hyperechogenic cases. This may also be an in utero indication of subsequent intrauterine and neonatal complications, such as cesarean section because of fetal distress (43%), treatment in a neonatal intensive care unit (51%) or increased perinatal mortality (5.4%, as compared with 0.8-1.0% in the normal population). Detailed ultrasound and Doppler examinations of renal parenchyma and arteries appear to be useful methods in the prenatal diagnosis of reduced renal perfusion and of intrauterine hypoxia to detect possible pathological fetal conditions in utero. [less ▲]

Assisted reproductive treatments (ART) hold an increasing place in the field of female infertility but also of male infertility with the development of new micromanipulative technologies. From January ... [more ▼]

Assisted reproductive treatments (ART) hold an increasing place in the field of female infertility but also of male infertility with the development of new micromanipulative technologies. From January 1985 to December 1997, more than 3,000 ovarian punctures were achieved at the CPMA of the University of Liege and more than 40,000 oocytes were recovered. Global results show a take home baby rate of 23% per ovum pick-up and 27% per embryo transfer. Embryo cryopreservation offers an efficient solution to the problem of supernumerary embryos and opens the way for IVF-derived procedures such as oocyte or embryo donation, surrogate mother. The transfer of frozen-thawed embryos increases the total ongoing pregnancy rate per cycle of 31%. One of the aims of our Centre in the near future is the development of new technologies such as control of chromosomal abnormalities or genetic defect in preimplantation embryos and clinical applications of oocyte or ovarian tissue freezing. [less ▲]

Human placentation is mediated by fetal trophoblastic cells which penetrate into the decidualized uterine endometrium. Trophoblast invasion requires the precisely regulated secretion of specific proteinases able to degrade the endometrial basement membranes and extracellular matrix. To document further the involvement of these proteinases during human placentation, we evaluated in vivo the expression of stromelysin-3, a member of the metalloproteinase family, during the first and third trimesters of pregnancy, by means of immunohistochemistry, in situ hybridization and Northern blot analysis. Human extravillous trophoblasts invading the maternal decidua produced stromelysin-3 during both, the first and third trimesters of pregnancy, but to a lesser extent during the latter. In floating villi, stromelysin-3 expression was restricted to the syncytiotrophoblasts that line intervillous vascular spaces. In conclusion, stromelysin-3 is expressed by differentiated, non-proliferative villous and extravillous trophoblastic cells in early and late placental beds and villi, and its pattern of expression evolves during pregnancy. Our observations suggest that stromelysin-3 could play a role in human placentation. [less ▲]

BACKGROUND: Human placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. EXPERIMENTAL DESIGN: Several studies have documented the key roles of matrix metalloproteinases and their tissue inhibitors in the invasion of various matrices by cultured trophoblasts. In vitro studies suggest that placentation could result from a balance between the secretion of these enzymes by trophoblast cells and their inhibition by the natural tissue inhibitors (TIMPs) produced by maternal decidual cells. The precise localization and levels of expression of these proteins that account for and control invasion during human placentation in vivo however, have not been described. We have evaluated, in vivo, by immunohistochemistry, Northern blot analysis and in situ hybridization, the expression of two metalloproteinases (gelatinases A and B) and their two tissue inhibitors (TIMPs 1 and 2) in placental villi and placental beds of first and third trimesters of normal pregnancy. RESULTS: Human first trimester intermediate trophoblast produced both gelatinases A and B; these two gelatinases were respectively less and no more detected at term in these cells. We found that both TIMP1 and 2 were also expressed in maternal decidual cells with a dramatic increase of TIMP1 at the term of pregnancy. In floating villi, gelatinase A and TIMP1 were localized in the stromal compartment, whereas gelatinase B and TIMP2 were codistributed in trophoblast cells. CONCLUSIONS: The gelatinases A and B and their tissue inhibitors are thus expressed by specific cells in early and late placental beds and villi. This pattern of expression varies during pregnancy. Therefore, our morphologic study supports biologic findings suggesting that these proteins may participate in placentation. [less ▲]

We present four children from two families with the typical 11q- phenotype resulting from an unbalanced segregation of a parental translocation. In the first family, the father had a 46,XY,t(5;11)(q24;q23 ... [more ▼]

We present four children from two families with the typical 11q- phenotype resulting from an unbalanced segregation of a parental translocation. In the first family, the father had a 46,XY,t(5;11)(q24;q23.3) constitution. The father of the three other children had a 46,XY,t(11;17)(q23;p13) translocation. Despite associated partial deletion, three of the children had a typical 11q- phenotype. The fourth one, whose pregnancy was terminated in the second trimester, had a hypoplastic left heart but no other considered gross anomalies. A review of 36 previous cases, including 5 due to translocations (4 familial rearrangements, and 1 of unknown origin) is given with emphasis on the relationships between break-points and phenotype. Undescribed manifestations in our patients include agenesis of corpus callosum adactyly and malrotation of the gut. [less ▲]

CD34-positive cells were isolated from a total of 23 cords using CellPro Ceprate columns. AIS MicroCellector flasks, and panning. The cells were (1) expanded in serum-free culture supplemented with a ... [more ▼]

CD34-positive cells were isolated from a total of 23 cords using CellPro Ceprate columns. AIS MicroCellector flasks, and panning. The cells were (1) expanded in serum-free culture supplemented with a variety of combinations of cytokines and (2) immunophenotyped using multiple fluorochrome labeling. The results indicated that the avidin column produced the highest purity of CD34-positive cells, and that immature blast cells could be expanded in serum-free culture. Preliminary results suggested that the four fluorochrome labeling technique may provide useful information on the lineage commitment of cord blood precursor and blast cells. [less ▲]

in International Journal of Developmental Biology (1992), 36(3), 451-3

Histological specimens of recent implantation sites are the basis of our current concept on human embryo implantation and placental development. In the Carnegie Collection maternal red blood cells were ... [more ▼]

Histological specimens of recent implantation sites are the basis of our current concept on human embryo implantation and placental development. In the Carnegie Collection maternal red blood cells were detected early in the primitive intervillous space (10th-12th day after conception). These cells were localized to the trophoblastic lacunae and originated from distended peripheral maternal sinusoids (Kaufmann, 1981). The classical theory states that progressively more and more maternal vessels are tapped. A true maternal blood flow is established around the 29th day. Dynamic investigations of human placental development in vivo are scarce and hampered by ethical considerations and the absolute requirement to refrain from using non aggressive and potentially harmful techniques. Despite these limitations such studies provide new insights that surprisingly contradict our previously and seemingly definitely established knowledge of the early phases of placental vascularization, and lead us to conclude that there is an absence of maternal blood circulation in the intervillous placental space (IVS) during the 12 first weeks of human pregnancy. [less ▲]

We report the prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in a 24-week-old fetus. Echographic features included cystic hygroma, a complex heart defect with right ventricular hypoplasia, and a ... [more ▼]

We report the prenatal diagnosis of Wolf-Hirschhorn syndrome (4p-) in a 24-week-old fetus. Echographic features included cystic hygroma, a complex heart defect with right ventricular hypoplasia, and a large placental chorioangioma. We suggest that chorioangioma may be associated with chromosomal imbalance and that systematic careful morphologic examination of the fetus and karyotyping of any pregnancy in which large chorioangioma is detected is advisable. Jugular lymphatic obstruction sequence has not been reported so far in association with 4p-syndrome. [less ▲]

A 46,XX;47,XX,+9;47,XX,+?mar karyotype was detected in an amniotic fluid cell culture and confirmed in a subsequent fetal blood sample from a 40-year-old woman. After termination of the pregnancy, none of ... [more ▼]

A 46,XX;47,XX,+9;47,XX,+?mar karyotype was detected in an amniotic fluid cell culture and confirmed in a subsequent fetal blood sample from a 40-year-old woman. After termination of the pregnancy, none of the 186 mitoses obtained from a second blood sample was trisomic for chromosome 9 (p less than 0.001). Selection against cells containing trisomy 9 is postulated to explain the disappearance of the lymphocyte clone. [less ▲]